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With the help of an electron microscope, OHSU researchers from Portland, Oregon, generated a three-dimensional model of the human epithelial sodium channel. The channel is essential in the control of blood pressure, among other functions in the body. Credit: OHSU
New research reveals for the first time the three-dimensional structure of a membrane channel essential for the control of blood pressure.
The results, published today in the open access journal eLife, represents the first time that the human epithelial sodium channel has been shown so precisely since it was isolated for the first time and described by cloning expression in 1993, said lead author Isabelle Baconguis, Ph.D., assistant professor at the OHSU Institute of Vollum. Lead author Sigrid Noreng, a graduate student at Baconguis Laboratory, added that this discovery provides a starting point for the development of better treatments for a range of diseases associated with the channel.
"It will certainly move the field forward," admitted Baconguis.
The channel allows sodium ions to be absorbed into the tissues of the entire body, including the kidney. As such, it is a crucial aspect of human health by regulating the balance of sodium, blood volume and blood pressure.
"We could not have left the ocean without her," joked co-author Richard Posert, a student at Baconguis Lab.
Sodium epithelial canal dysfunction, or ENaC, can lead to severe forms of hypertension, such as Liddle's syndrome or neonatal salt disorder. The discovery addresses fundamental biophysical questions about the specific architecture of the channel, which could lead to the development of drugs to improve the treatment of diseases such as severe hypertension, heart failure and nephrotic syndrome.
"It's the first visual representation of a protein that is linked to many diseases," Baconguis said. "As soon as you disrupt this membrane protein, everything downstream is also disrupted."
Noreng noted that the discovery may be particularly useful in developing targeted drugs to control high blood pressure.
"There are no good drugs that specifically target this protein," said Noreng. "The discovery of the structure of this channel will be very important for the development of new and better drugs for blood pressure."
The researchers made this discovery through the use of a cryo-electron electron microscope installed in the Robertson Life Sciences Building building of the OHSU. Cryo-EM technology is part of a new national center intended to expand the use of a technique that is revolutionizing structural biology. The technique allows scientists to visualize biological molecules at the atomic scale and see them in their natural state.
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More information:
Sigrid Noreng et al, Structure of the human epithelial sodium channel by cryoelectronic microscopy, eLife (2018). DOI: 10.7554 / eLife.39340
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